Single-cell RNA sequencing reveals that targeting HSP90 suppresses PDAC progression by restraining mitochondrial bioenergetics
Hu Li-Peng, Zhou Kai-Xia, Huo Yan-Miao, Liu De-Jun, Li Qing, Yang Min-Wei, Huang Pei-Qi, Xu Chun-Jie, Tian Guang-Ang, Yao Lin-Li, Zhang Xue-Li, Wang Ya-Hui, Li Jun, Zhang Zhi-Gang, Jiang Shu-Heng, Xi
Journal：Oncogenesis
IF：7.49
DOI：10.1038/s41389-021-00311-4
PMID：33658487
Published：2021-03-03
research field：分子生物学药理学干细胞研究再生医学肺病学
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective treatment strategies. There is an urgent need for the development of new strategies for PDAC therapy. The genetic and phenotypic heterogeneity of PDAC cancer cell populations poses further challenges in the clinical management of PDAC. In this study, we performed single-cell RNA sequencing to characterize PDAC tumors from KPC mice. Functional studies and clinical analysis showed that PDAC cluster 2 cells with highly Hsp90 expression is much more aggressive than the other clusters. Genetic and pharmacologic inhibition of Hsp90 impaired tumor cell growth both in vitro and in vivo. Further mechanistic study revealed that HSP90 inhibition disrupted the interaction between HSP90 and OPA1, leading to a reduction in mitochondrial cristae amount and mitochondrial energy production. Collectively, our study reveals that HSP90 might be a potential therapeutic target for PDAC.
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